1. Field of the Invention
The present invention relates to a method and apparatus for producing dry particles. More particularly, the present invention relates to a method and apparatus for producing dry particles that are suitable for inhalation into the lung, and which contain an active agent.
2. Related Art
Delivery of drugs and other active agents can be accomplished through the use of dry powder compositions made from particles containing the drug or active agent. In producing such particles, it is often desirable to combine substances with significantly different physical properties to achieve the desired pharmaceutical effect in patients. Moreover, it is often desirable to produce particles that are a combination of different substances. One way to produce particles containing a combination of different substances is to dissolve the substances in suitable solvents, and then remove the solvents by, for example, evaporation or drying, to yield the desired particles. A major difficulty with this approach is that substances with differing physical properties often have very different solubilities in solvents. Consequently, co-solvents, or a larger mixture of solvents, may be needed to form the solution from which the particles are produced. However, the use of co-solvents can cause degradation of one of the components, through chemical or physical incompatibility of the components in solution.
One example of the incompatibility of components is the production of particles that contain a hydrophobic component and a hydrophilic component. The production of such particles is described in U.S. Pat. No. 6,077,543 to Gordon et al. (“the Gordon patent”). As described in the Gordon patent, a hydrophobic drug solution and a hydrophilic excipient solution are spray dried together to form dry powders containing the drug and the excipient. To solve the incompatibility between the hydrophobic and hydrophilic components, the hydrophilic and hydrophobic components are separately dissolved in different solvents, and separately directed simultaneously through a nozzle into a spray dryer. In this method, the two liquid components are separately delivered to the nozzle that atomizes the two liquid components into droplets that are dried in a spray dryer to form dry particles.
One of the drawbacks of the method and apparatus of the Gordon patent is that there is no complete mixing of the two liquid components before being atomized into droplets. Thus, the droplets that are produced are unlikely to be a homogeneous mixture of the two liquid components, nor is there likely to be uniformity among the droplets. Consequently, the particles that are produced are unlikely to contain a homogeneous mixture of the drug and excipients, and are unlikely to have uniformity among the particles themselves. Thus, there is a need in the art for an improved method and apparatus for producing dry particles that contain a homogenous mixture of drug and excipient components, with improved uniformity among the particles. There is a particular need in the art for such a method and apparatus where the drug component and excipient component are physically or chemically incompatible in the liquid state.
One important application for dry powder compositions is pulmonary drug delivery. Several properties of the dry particles have been identified that correlate with enhanced delivery to the pulmonary system. For example, it has been found that particles having a tap density less than 0.4 g/cm3 and an aerodynamic diameter that is between about 1 and about 3 microns (μm) are well suited for delivery to the alveoli or the deep lung. If delivery to the central or upper airways is desired, particles having larger aerodynamic diameters, ranging for example, from about 3 to about 5 microns are preferred. Furthermore, particles having a geometric diameter greater than about 5 microns are believed to more successfully avoid phagocytic engulfment by alveolar macrophages and clearance from the lungs.
There is a need in the art for improved methods for producing particles having selected geometric and aerodynamic sizes optimized for delivery to targeted sites of the pulmonary system. There is a particular need for an apparatus and method that allows for optimization of particle size in real-time, during the particle production process.
The apparatus and method of the present invention, a description of which is fully set forth below, solve the aforementioned problems and difficulties with conventional approaches to producing dry powder compositions.